FDA Approves Olaparib Tablets for Ovarian Cancer

The FDA has approved olaparib tablets (Lynparza) as a maintenance therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.

The approval was based on data from the phase III SOLO2 trial and the phase II Study 19 trial. In SOLO2, maintenance treatment with olaparib showed a 70% reduction in the risk of progression or death compared with placebo for patients with platinum-sensitive, relapsed, BRCA-mutant ovarian cancer. In Study 19, the risk of progression or death was reduced by 65% with maintenance olaparib versus placebo for women with ovarian cancer, regardless of BRCA status.

The FDA noted that the olaparib tablets and capsules were not interchangeable, and that the capsules were being phased out of the US market. According to the FDA, olaparib capsules will only be available through the Lynparza Specialty Pharmacy Network. Olaparib capsules were initially approved in 2014 for the treatment of women with BRCA-positive advanced ovarian cancer following treatment with 3 or more prior lines of chemotherapy. The tablets are now also approved for this indication.

“Today’s approval is welcome news for US patients with ovarian cancer, who are now able to benefit from treatment with olaparib irrespective of their BRCA mutation status," lead investigator of the SOLO2 study Eric Pujade-Lauraine, MD, PhD, head of the Women Cancers and Clinical Research Department at Hôpitaux Universitaires Paris Centre, site Hôtel-Dieu, said in a statement. "This latest regulatory milestone underscores the breadth and depth of clinical data on olaparib, and not only demonstrates its efficacy as maintenance therapy, but adds to the data presented earlier this year showing sustained quality of life for patients undergoing treatment for this serious disease.”

In the SOLO2 trial,1 patients were randomized 2:1 to olaparib as a 300-mg tablet twice daily (n = 196) or placebo (n = 99). All patients had relapsed ovarian cancer, confirmed BRCA1/2 mutation, and were in response to their most recent platinum-containing regimen following 2 or more prior systemic regimens. The primary endpoint was investigator-assessed progression-free survival (PFS).

The median age of patients was 56 years and baseline characteristics did not differ substantively between treatment groups. Most patients had an ECOG performance status of 0 (83% with olaparib vs 78% for placebo) and 47% of patients had a complete response to prior chemotherapy. Prior bevacizumab was received by 17% of those in the olaparib group and for 20% of those in the placebo arm. Approximately 40% of patients had received 3 or more prior lines of therapy.

The median investigator-assessed PFS was 19.1 months compared with 5.5 months in the placebo arm (HR, 0.30; 95% CI, 0.22-0.41; P <.0001). A prespecified analysis of PFS by a blinded central review committee showed a median PFS of 30.2 months for the olaparib group versus 5.5 months for placebo, a 75% reduction in the hazard for progression and death (HR, 0.25; 95% CI, 0.18-0.35; P <.0001).

The median PFS for patients taking maintenance olaparib was 8.4 months, compared to 4.8 months for the control group (HR, 0.35; P <.0001). For those with BRCA mutations, the median PFS was 11.2 versus 4.3 months for placebo, representing an 82% reduction in the risk of progression or death (HR, 0.18; P <.0001).

In the third interim analysis of Study 19, across the full study the median OS was 29.8 months in the olaparib group and 27.8 months in the placebo group (HR, 0.73; 95% CI, 0.55-0.96; nominal P = .02483). In the BRCA mutation group (n = 136), median OS was 34.9 months for the olaparib group and 30.2 months for placebo (HR, 0.62; 95% CI, 0.41-0.94; nominal P = .02480). However, these were not considered to be statistically significant.

According to the FDA, the most commonly observed adverse events (AEs) for olaparib were anemia, nausea, fatigue (including asthenia), vomiting, nasopharyngitis, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, and stomatitis. The most common laboratory abnormalities were decrease in hemoglobin, increase in mean corpuscular volume, decrease in lymphocytes, decrease in leukocytes, decrease in absolute neutrophil count, increase in serum creatinine, and decrease in platelets.

In the SOLO2 trial, which assessed the tablets specifically, grade ≥3 AEs were reported for 36.9% of patients treated with olaparib versus 18.2% with placebo. The most common non-hematologic AEs for olaparib were nausea (75.9%), fatigue/asthenia (65.6%), vomiting (37.4%), diarrhea (32.8%), and abdominal pain (24.1%). The incidence of serious hematologic AEs included anemia (19.5%), neutropenia (5.1%), and thrombocytopenia (1.0%).

The median duration of treatment was 19.4 months for olaparib versus 5.6 months with placebo. Forty-five percent of patients required a dose interruption in the olaparib group versus 18% in the placebo arm and dose reductions were required for 27% and 3% of patients, respectively. The most frequent AEs leading to dose interruption or reduction were anemia (22%), neutropenia (9%), and fatigue/asthenia (8%).